Provided are anti-BMP4 antibodies binding to a conformational epitope located within the BMPRla binding site of BMP4 and pharmaceutical uses thereof.
Figure 1 Anti-BMP4 VHH specificity to the different BMPs.
Phosphorylation of SMAD1/5/8 in EPC2-hERT cells after activation with 100 ng/mL of human BMP4 in the presence of 5 mg/mL VHHs.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
Figure 2 Anti-BMP4 VHH specificity to the different BMPs.
C2C12 cells were activated with human BMPs in the presence or absence of 5 mg/mL of VHHs or human Fc-Noggin.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
Figure 3 IC50 curves of VHH biheads and monoheads.
C2C12 cells were activated with human BMP4 at 5 ng/mL with increasing concentrations of VHHs.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
Figure 4 Kinetic analysis for BMP binding.
Binding of VHHs to the different BMPs was tested in a direct SPR assay.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
Figure 5 Kinetic analysis for BMP binding.
Epitope binning of VHH-coated chip plates. BMP4 (1.0 mg/mL) was injected on the chip followed by the injection of a second VHH (2.0 mg/mL) or the corresponding controls.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
Figure 6 HADDOCK docking of the VHHs to BMP4 binding.
Function of the generated mutant variants in inhibiting ID1 promoter activity in C2C12 cells after stimulation with BMP4 (5 ng/mL) for 16 hours.
Calpe, S., Wagner, K., El Khattabi, M., Rutten, L., Zimberlin, C., Dolk, E., ... & Krishnadath, K. K. (2015). Effective inhibition of bone morphogenetic protein function by highly specific llama-derived antibodies. Molecular cancer therapeutics, 14(11), 2527-2540.
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MOB-2244z | Mouse Anti-BMP4 Recombinant Antibody (clone 18H6) | WB, ELISA, FC, ICC, IHC | Mouse IgG1 |
ZG-0339F | Mouse Anti-BMP4 Recombinant Antibody (ZG-0339F) | WB, ELISA | Mouse IgG |
VS3-QX123 | Mouse Anti-BMP4 Recombinant Antibody (clone 1C-17) | WB, ICC, FC | Mouse IgG1 |
VS3-QX124 | Mouse Anti-BMP4 Recombinant Antibody (clone 10F4B4) | WB, IHC, ICC, FC, ELISA | Mouse IgG1 |
VS4-WK50 | Rabbit Anti-BMP4 Recombinant Antibody (clone 19B7) | ELISA, WB, IF | Rabbit IgG |
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